A mass spectrometer is an instrument used in an analytical technique of mass spectrometry to analyze a composition of a sample material or a chemical specimen. Mass spectrometry is able to measure or otherwise determine, at least, relative concentrations of components (such as atoms and/or molecules) that form the specimen. The specimen, typically in gas form, is ionized by a flow of high-energy electrons, transforming atoms and/or molecules of the specimen into various kinds of ions. Each kind of the ions may have a specific mass-to-charge ratio (hereinafter “m/z”). The ionized specimen (hereinafter “ion flow”) is then accelerated electrically to enter into a filter, which passes only some ions (hereinafter the “selected ions”) in the ion flow that exhibit certain m/z, while blocking others. The selected ions, after passing the filter, arrive at an electrode, where charges carried by the selected ions are collected and form a current (hereinafter “ion current”) that flows to a detection circuit/subsystem. The detection circuit measures the ion current, and designates a magnitude of the ion current as a representation of an abundance of a certain kind of atoms and/or molecules associated with passing ions. The filter is commonly realized by a quadrupole mass filter (QMF). The m/z of the ions that are passable by a QMF is typically determined by one or more radio-frequency (RF) and/or direct-current (DC) voltages applied to the QMF. The mass spectrometer is configured to adjust the RF and DC voltages of the QMF, thereby changing the passible ions from ions of a specific m/z to ions of a different m/z. With this process repeated for different m/z values, the relative concentrations of atoms and/or molecules that form the specimen can be revealed.
A challenging problem encountered in design and implementation of a mass spectrometer, among others, resides in how the detection circuit can accurately and efficiently detect the ion current, which may vary over a large dynamic range. Depending on the amount of the specimen (measured in, for example, numbers of mole) and the relative concentration of a specific kind of ion in the specimen, an ion current may be as large as 100 nano-ampere (nA), or 10−7 A, and as small as 10 femto-ampere (fA), or 1014 A. Namely, a dynamic range of the ion current may be as large as seven orders of magnitude, if not more. The detection circuit thus needs to be capable of detecting ion currents over this large dynamic range, which readily imposes a stringent design requirement. On top of that, detecting a minute current in the fA range imposes another stringent design requirement. Electronic circuits are subjected to various kinds of noise sources in the system they are designed to serve, and this is especially true for a mass spectrometer. At least the generation of the high-energy electron flow, the ionization of the gas specimen, the acceleration of the ion flow and the operation of the QMF all employ high-voltage, high-power and/or high-frequency oscillating voltage sources. These voltages sources could easily couple electrical noise to the sensitive detection circuits, disturbing the electrical signals therein and affecting the measurement result.
FIG. 1 depicts a schematic diagram of an ion current detection circuit 100 that is commonly used in a mass spectrometer. Detection circuit 100 includes an operational amplifier (op-amp) 110, a positive input terminal of which is connected to electrical ground. Feedback capacitor C11 is provided for feedback stability of detection circuit 100, the value of which is typically in the range of 10 femto-farad (fF) to 100 fF. Capacitor C11 is connected between an output terminal of op-amp 110 and a negative input terminal of op-amp 110. Resistors R11 and R12 are gain resistors. While resistor R11 is fixedly connected in parallel with capacitor C11, resistor R12 is configured to connect in parallel with capacitor C11 and resistor R11 when switch S12 is closed or otherwise turned on. When switch S12 is open or otherwise turned off, resistor R12 is not electrically connected with detection circuit 100 and thus does not participate in the operation of detection circuit 100. Ion current 105 that is collected on a collecting electrode of the mass spectrometer flows into detection circuit 100 through input node 101, and through resistor R11 (and resistor R12 if switch S12 is on). While flowing through resistors R11 and R12, ion current 105 is converted into output voltage (hereinafter “Vout”) 115. Specifically, with R representing the total resistance between the output terminal and the negative input terminal of op-amp 110, and I representing a magnitude of ion current 105, detection circuit 100 would generate an output voltage Vout=I·R. Namely, Vout is proportional to I with a gain of R, and thus represents or otherwise corresponds to the magnitude of ion current 105. Alternatively speaking, ion current 105 can be back calculated as I=Vout/R, and interpreted as an indication of an abundance of a specific kind of ion or molecule in a specimen being analyzed by the mass spectrometer. The gain of R is programmable through switch S12, thereby providing various gain settings of detection circuit 100. For example, when S12 is open, R=R11. When S12 is closed, R=R11//R12 (the composite resistance of R11 in parallel with R12). The different gain settings may be useful for different levels of ion current 105. For example, a weaker ion current 105 may require a larger gain setting, while a stronger ion current 105 may do fine with a smaller gain setting.
In practical applications, detection circuit 100 of FIG. 1 suffers numerous limitations. First of all, it is difficult for detection circuit 100 to accurately detect a weak ion current 105. Apparently, it is not possible to detect an arbitrarily infinitesimal signal. In general, for any electronic detection circuit, there exist various sources of noise and circuit offsets that collectively determine a minimum detectable level of the detection circuit, or “noise floor”, below which the detection circuit is not able to distinguish a signal intended to be detected from the noise the circuit is susceptible to. That is, when the noise floor is higher than the signal to be detected, the signal is “buried” under the noise floor and cannot be detected by the circuit. Detection circuit 100 realized in discrete electronic components typically has a noise floor of 300 micro-volts (uV) or so. With a gain setting practically limited to 6e9 (that is, 6,000,000,000) or so, the noise floor of 300 uV limits the smallest detectable ion current to be around 50 fA for detection circuit 100. That is, detection circuit 100 may not be able to detect ion current 105 if ion current 105 is around or below 50 fA. Using a gain setting higher than 6e9 would require a gain resistor that may be too large to fit into a miniaturized mass spectrometer, and/or the high-value gain resistor may need to have a larger error in resistance value, not to mention that a high-value gain resistor would become a major noise source in detection circuit 100 and significantly raise the noise floor. Thus, using a gain resistor of a higher value may not only fail to extend the detectable range of detection circuit 100 below 50 fA, but actually reversely impact the minimum detectable current level of detection circuit 100. In practical situations, however, a high-performance mass spectrometer is often required to detect an ion current as low as 10 fA or so. Detection circuit 100 is thus not able to meet the requirement.
Secondly, detection circuit 100 often suffers a slow detection process due to a long waiting period in practical detection situations. Each of waiting periods 232 and 234 shown in FIG. 2 is an example of the long waiting period, with waiting period 232 longer than waiting period 234. FIG. 2 shows graph 210, of ion current 105, and graph 220, of Vout 115, for detection circuit 100 of FIG. 1. Specifically, graph 210 shows two ion current waveforms, 212 and 214, while graph 220 shows two Vout waveforms, 222 and 224. When ion current 105 of waveform 212 is received at input node 101, a corresponding Vout of waveform 222 is generated at the output terminal of op-amp 110. Similarly, when ion current 105 of waveform 214 is received at input node 101, a corresponding Vout of waveform 224 is generated at the output terminal of op-amp 110. Each set of ion current and Vout waveforms may represent ions of a respective m/z. That is, waveforms 212 and 222 may result from ions of a specific value of m/z, while waveforms 214 and 224 may result from ions of a different value of m/z.
The reason for a possible long waiting period of detection circuit 100, as implemented in a mass spectrometer, is explained below. When the QMF is adjusted from passing ions of a first value of m/z (hereinafter “(m/z)1”) to passing ions of a second value of m/z, (hereinafter “(m/z)2”), the transition normally results in a transient or temporary perturbation to the ion current caused by capacitive coupling from various sources in the mass spectrometer, and is often manifested as one or more large peaks or valleys, or both, in the waveform of the ion current. A measurement of the ion current during this transitional phase of peaks and valleys may result in an erroneous reading of the actual ion current of (m/z)2. To get an accurate measurement of the (m/z)2 ion current, the detection circuit of the mass spectrometer may need to wait until this temporary perturbation has settled. This waiting period for the ion current to settle may be a hundred times longer, or even more, than the actual measurement time after the ion current has settled. The long waiting period, during which the ion current detection would not yield representative results, drastically slows down the process of ion current detection in the mass spectrometer.
This phenomenon is clearly shown in FIG. 2, wherein each of ion current waveforms 212 and 214 and each of Vout waveforms 222 and 224 shows an initial period of peaks and valleys. For example, the QMF of the mass spectrometer may have just changed from (m/z)1 to (m/z)2 at time t0, resulting in waveform 212 and waveform 222 which represent the corresponding ion current 105 and Vout 115, respectively. Waveform 212 and waveform 222 have a shape similar to one another, as they are related by the gain of R as defined in the linear equation of Vout=I·R, as previously presented. Each of waveforms 212 and 222 exhibits relatively large peaks and valleys between times t0 and t3, and does not settle until time t3. Consequently, detection circuit 100 would need to wait for a waiting period 232, which has a length of (t3˜t0), before giving a representative value, v2, of the ion current of (m/z)2. The actual detection time for the representative value v2 is shown as detection period 242, which has a length of (t4˜t3). Similarly, the QMF of the mass spectrometer may have just changed from a third value of m/z, (hereinafter “(m/z)3”) to a fourth value of m/z, (hereinafter “(m/z)4”) at time t0, resulting in waveform 214 and waveform 224 which represent the corresponding ion current 105 and Vout 115, respectively. Waveform 214 and waveform 224 also have a similar shape to one another, as they are also related by the gain of R as defined in the linear equation of Vout=I·R. Each of waveforms 214 and 224 exhibits relatively large peaks and valleys between times t0 and t1, and does not settle until time t1. Consequently, detection circuit 100 would need to wait for a waiting period 234, which has a length of (t1−t0), before giving a representative value, v4, of the ion current of (m/z)4. The actual detection time for the representative value v4 is shown as detection period 244, which has a length of (t2−t1). Typically, detection periods 242 and 244, usually of a few milliseconds, may have a same length, which is deterministic by the design of the detection circuit. In contrast, waiting periods 232 and 234 may have different lengths, which tend to be less controlled or otherwise less predictable, and usually in the range of tens even hundreds of milliseconds. That is, most of the time for the ion current detection of the spectrometer is consumed by the waiting periods 232 and 234, instead of by the actual detection periods 242 and 244.
It is worth noting that in each of graphs 210 and 220 of FIG. 2, the time axis is normalized with respect to the time when an adjustment is made to the QMF of the mass spectrometer to pass ions of a different m/z value. That is, for waveforms 212 and 222, t0 represents the time when a QMF setting is changed from (m/z)1 to (m/z)2. Likewise, for waveforms 214 and 224, t0 represents the time when a QMF setting is changed from (m/z)3 to (m/z)4. Since a mass spectrometer typically has only one QMF, waveforms 212 and 222 cannot be generated at the same time as waveforms 214 and 224. The two sets of waveforms need to be generated separately at two distinctive points in time, or in “two distinctive scans” of the sample specimen. Therefore, waveforms 212 and 214 ought not to be interpreted as happening concurrently, and waveforms 222 and 224 ought not to be interpreted as happening concurrently.
It is also worth noting that noise floor 201 of detection circuit 100 is shown in graph 220 of FIG. 2. As discussed previously, a Vout 115 of a value lower than noise floor 201 will not be detected by detection circuit 100. Take waveform 224 for example. Waveform 224 may be detectable for some time during waiting period 234, as waveform 224 is higher than noise floor 201 corresponding to value Vmin, for a portion of waiting period 234. However, waveform 224 is completely below noise floor 201 after settling at t1, and thus undetectable. Namely, while detection circuit 100 is supposed to detect the representative value of v4 for Vout 115 during detection period 244, in reality detection circuit 100 is not able to detect value v4, given the fact that v4 is below Vmin. Instead, detection circuit 100 would detect Vout 115 as simply 0 volt.
When detection circuit 100 detects Vout 115 to be very small or close to 0, detection circuit 100 may attempt to increase a gain setting of detection circuit 100 to see if a larger Vout 115 can be resulted. As mentioned previously, the gain setting of detection circuit 100 is determined by the total resistance R between the output terminal and the negative input terminal of op-amp 110. By increasing the total resistance R between the output terminal and the negative input terminal of op-amp 110, a higher gain will be applied to ion current 105, and a higher Vout 115 will be resulted, which may thus become higher than noise floor 201 and become detectable by detection circuit 100.
FIG. 3 shows various waveforms of Vout 115 that correspond to a same waveform 311 of ion current 105 under various gain settings (i.e., various values of R) of detection circuit 100. Governed by the linear equation of Vout=I·R, as previously discussed, a higher gain setting results in a higher value of Vout 115. That is, waveform 322 corresponds to a higher R value than waveform 321, while waveform 323 corresponds to a higher R value than waveform 322. Likewise, waveform 323 corresponds to a higher R value than waveform 322, and waveform 324 corresponds to a higher R value than waveform 323, whereas waveform 325 corresponds to a higher R value than waveform 324.
It is worth noting that, among waveforms 321-325 of FIG. 3, only waveforms 322, 323 and 324 are detectable by detection circuit 100. As discussed above, waveform 321 is undetectable, since waveform 321 corresponds to a Vout of value v1 that is below noise floor 301 of value Vmin. In addition, waveform 325 is also undetectable, and that is because waveform 325 corresponds to a Vout of value v5 that is above saturation threshold 399 of value Vmax. Saturation threshold 399 of value Vmax represents a maximal detectable voltage of Vout 115 for detection circuit 100. When Vout 115 is above Vmax, circuit 100 may saturate and thus not function as desired (e.g., the high open-loop gain of op-amp 110 may no longer be maintained), and the linear relationship of Vout=I·R between Vout 115 and ion current 105 may not be truthfully maintained. Namely, when Vout 115 is detected to be at or above Vmax, the back calculation of I=Vout/R may no longer be valid. Both waveforms 321 and 325 are referred to as “out of range”, or “OOR” in short, as they are out of the detectable range of Vout within which detection circuit 100 is designed to work properly.
A way for detection circuit 100 to move a waveform from a state of OOR into the detectable range between Vmin and Vmax is by changing the gain setting R of detection circuit 100. For example, Vout 115 may move from waveform 321 to any of the waveforms 322, 323 and 324 by increasing the total resistance R between the output terminal and the negative input terminal of op-amp 110. Similarly, Vout 115 may move from waveform 325 to any of the waveforms 322, 323 and 324 by decreasing the total resistance R between the output terminal and the negative input terminal of op-amp 110. The total resistance R may be decreased or increased by turning on or off switch S12 of FIG. 1. The change of resistance R, however, gives rise to another limitation of detection circuit 100: it is a slow process for detection circuit 100 to move from a gain setting to a different gain setting. Specifically, to provide a high gain for detecting weak ion current in the fA range, detection circuit 100 is required to use high value resistors, such as R1 and R2 of FIG. 1. The high value resistors would result in large time constants for detection circuit 100, making changing the gain setting a slow process. For example, it may take hundreds of milliseconds for Vout 115 to settle after detection circuit 100 changes the gain setting.
For the same reason, detection circuit 100 is slow to respond to a sudden surge in ion current 105. In practical operation of a mass spectrometer, occasionally there may be a dramatically high concentration of certain ions in the ion flow. The high concentration of ions may pass the QMF, causing a temporarily high level of ion current 105, or a “sudden surge”. The sudden surge may temporarily saturate detection circuit 110, causing Vout 115 to enter an OOR state. Although a change in gain setting may not be required to deal with the sudden surge, as the sudden surge will eventually pass, due to the long time constants described above detection circuit 100 would be slow in recovering from the saturation and coming out the OOR state.
In addition to the limitations stated above, there are other secondary reasons why a traditional detection circuit of a mass spectrometer, such as detection circuit 100 of FIG. 1, suffers from high noise and low speed. For example, since the magnitude of ion current 105 is represented by the measured absolute value of Vout 115, detection circuit 100 requires the use of op-amp 110 that has a very high open-loop gain. Op-amp 110 that exhibits a very high open-loop gain typically suffers from a higher noise and a long recovery time from saturation.